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991.
992.
Introduction
Both the quantity and the distribution of health workers in a country are fundamental for assuring equitable access to health services. Using the case of Brazil, we measure changes in inequalities in the distribution of the health workforce and account for the sources of inequalities at sub-national level to identify whether policies have been effective in decreasing inequalities and increasing the density of health workers in the poorest areas between 1991 and 2005.Methods
With data from Datasus 2005 and the 1991 and 2000 Census we measure the Gini and the Theil T across the 4,267 Brazilian Minimum Comparable Areas (MCA) for 1991, 2000 and 2005 to investigate changes in inequalities in the densities of physicians; nurse professionals; nurse associates; and community health workers by states, poverty quintiles and urban-rural stratum to account for the sources of inequalities.Results
We find that inequalities have increased over time and that physicians and nurse professionals are the categories of health workers, which are more unequally distributed across MCA. The poorest states experience the highest shortage of health workers (below the national average) and have the highest inequalities in the distribution of physicians plus nurse professionals (above the national average) in the three years. Most of the staff in poor areas are unskilled health workers. Most of the overall inequalities in the distribution of health workers across MCA are due to inequalities within states, poverty quintiles and rural-urban stratum.Discussion
This study highlights some critical issues in terms of the geographical distribution of health workers, which are accessible to the poor and the new methods have given new insights to identify critical geographical areas in Brazil. Eliminating the gap in the health workforce would require policies and interventions to be conducted at the state level focused in poor and rural areas. 相似文献993.
Garza DR Thompson CC Loureiro EC Dutilh BE Inada DT Junior EC Cardoso JF Nunes MR de Lima CP Silvestre RV Nunes KN Santos EC Edwards RA Vicente AC de Sá Morais LL 《PloS one》2012,7(5):e37283
The 7th cholera pandemic reached Latin America in 1991, spreading from Peru to virtually all Latin American countries. During the late epidemic period, a strain that failed to ferment sucrose dominated cholera outbreaks in the Northern Brazilian Amazon region. In order to understand the genomic characteristics and the determinants of this altered sucrose fermenting phenotype, the genome of the strain IEC224 was sequenced. This paper reports a broad genomic study of this strain, showing its correlation with the major epidemic lineage. The potentially mobile genomic regions are shown to possess GC content deviation, and harbor the main V. cholera virulence genes. A novel bioinformatic approach was applied in order to identify the putative functions of hypothetical proteins, and was compared with the automatic annotation by RAST. The genome of a large bacteriophage was found to be integrated to the IEC224's alanine aminopeptidase gene. The presence of this phage is shown to be a common characteristic of the El Tor strains from the Latin American epidemic, as well as its putative ancestor from Angola. The defective sucrose fermenting phenotype is shown to be due to a single nucleotide insertion in the V. cholerae sucrose-specific transportation gene. This frame-shift mutation truncated a membrane protein, altering its structural pore-like conformation. Further, the identification of a common bacteriophage reinforces both the monophyletic and African-Origin hypotheses for the main causative agent of the 1991 Latin America cholera epidemics. 相似文献
994.
Sousa JA Oliveira IS Silva FV Costa DA Chaves MH Oliveira FA Nunes PH Oliveira RC 《Zeitschrift für Naturforschung. C, Journal of biosciences》2012,67(3-4):163-171
The Sterculia striata ethanolic extract (Ss-EtOH) inhibited gastric lesions induced by ethanol, HCl/ethanol, and ischemia/reperfusion, but not those induced by indomethacin, and did not alter the gastric secretion. Ss-EtOH restored the catalase activity and content of nonprotein sulfhydryl groups in the stomach of mice treated with ethanol. The gastroprotection induced by Ss-EtOH in the ethanol-induced gastric lesion model was abolished by N(G)-nitroL-arginine methyl ester (L-NAME) pretreatment, suggesting the involvement of nitric oxide and antioxidant compounds, but not prostaglandins, in this activity. Lupeol obtained from Ss-EtOH promoted gastroprotection as well as the extract at the same dose, and it must therefore contribute to the observed effects. 相似文献
995.
PN Pereira MP Dobreva E Maas FM Cornelis IM Moya L Umans CM Verfaillie A Camus SM de Sousa Lopes D Huylebroeck A Zwijsen 《Development (Cambridge, England)》2012,139(18):3343-3354
The strength and spatiotemporal activity of Nodal signaling is tightly controlled in early implantation mouse embryos, including by autoregulation and feedback loops, and involves secreted and intracellular antagonists. These control mechanisms, which are established at the extra-embryonic/embryonic interfaces, are essential for anterior-posterior patterning of the epiblast and correct positioning of the primitive streak. Formation of an ectopic primitive streak, or streak expansion, has previously been reported in mutants lacking antagonists that target Nodal signaling. Here, we demonstrate that loss-of-function of a major bone morphogenetic protein (BMP) effector, Smad5, results in formation of an ectopic primitive streak-like structure in mutant amnion accompanied by ectopic Nodal expression. This suggests that BMP/Smad5 signaling contributes to negative regulation of Nodal. In cultured cells, we find that BMP-activated Smad5 antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-Foxh1 autoregulatory pathway through the formation of an unusual BMP4-induced Smad complex containing Smad2 and Smad5. Quantitative expression analysis supports that ectopic Nodal expression in the Smad5 mutant amnion is induced by the Nodal autoregulatory loop and a slow positive-feedback loop. The latter involves BMP4 signaling and also induction of ectopic Wnt3. Ectopic activation of these Nodal feedback loops in the Smad5 mutant amnion results in the eventual formation of an ectopic primitive streak-like structure. We conclude that antagonism of Nodal signaling by BMP/Smad5 signaling prevents primitive streak formation in the amnion of normal mouse embryos. 相似文献
996.
Sousa EH Basso LA Santos DS Diógenes IC Longhinotti E Lopes LG Moreira Ide S 《Journal of biological inorganic chemistry》2012,17(2):275-283
Abstract
For over a decade, tuberculosis (TB) has been the leading cause of death among infectious diseases. Since the 1950s, isoniazid has been used as a front-line drug in the treatment of TB; however, resistant TB strains have limited its use. The major route of isoniazid resistance relies on KatG enzyme disruption, which does not promote an electron transfer reaction. Here, we investigated the reactivity of isoniazid metal complexes as prototypes for novel self-activating metallodrugs against TB with the aim to overcome resistance. Reactivity studies were conducted with hydrogen peroxide, hexacyanoferrate(III), and aquopentacyanoferrate(III). The latter species showed a preference for the inner-sphere electron transfer reaction pathway. Additionally, electron transfer reaction performed with either free isoniazid or (isoniazid)pentacyanoferrate(II) complex resulted in similar oxidized isoniazid derivatives as observed when the KatG enzyme was used. However, upon metal coordination, a significant enhancement in the formation of isonicotinic acid was observed compared with that of isonicotinamide. These results suggest that the pathway of a carbonyl-centered radical might be favored upon coordination to the Fe(II) owing to the π-back-bonding effect promoted by this metal center; therefore, the isoniazid metal complex could serve as a potential metallodrug. Enzymatic inhibition assays conducted with InhA showed that the cyanoferrate moiety is not the major player involved in this inhibition but the presence of isoniazid is required in this process. Other isoniazid metal complexes, [Ru(CN)5(izd)]3− and [Ru(NH3)5(izd)]2+ (where izd is isoniazid), were also unable to inhibit InhA, supporting our proposed self-activating mechanism of action. We propose that isoniazid reactivity can be rationally modulated by metal coordination chemistry, leading to the development of novel anti-TB metallodrugs. 相似文献997.
Ammonium is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
Here we show that in aging Saccharomyces cerevisiae (budding yeast) cells, NH(4) (+) induces cell death associated with shortening of chronological life span. This effect is positively correlated with the concentration of NH(4) (+) added to the culture medium and is particularly evident when cells are starved for auxotrophy-complementing amino acids. NH(4) (+)-induced cell death is accompanied by an initial small increase of apoptotic cells followed by extensive necrosis. Autophagy is inhibited by NH(4) (+), but this does not cause a decrease in cell viability. We propose that the toxic effects of NH(4) (+) are mediated by activation of PKA and TOR and inhibition of Sch9p. Our data show that NH(4) (+) induces cell death in aging cultures through the regulation of evolutionary conserved pathways. They may also provide new insights into longevity regulation in multicellular organisms and increase our understanding of human disorders such as hyperammonemia as well as effects of amino acid deprivation employed as a therapeutic strategy. 相似文献
998.
Human populations are constantly plagued by hematophagous insects' bites, in particular the triatomine insects that are vectors of the Trypanosoma cruzi agent in Chagas disease. The pharmacologically-active molecules present in the salivary glands of hematophagous insects are injected into the human skin to initiate acquisition of blood meals. Sets of vasodilators, anti-platelet aggregators, anti-coagulants, immunogenic polypeptides, anesthetics, odorants, antibiotics, and detoxifying molecules have been disclosed with the aid of proteomics and recombinant cDNA techniques. These molecules can provide insights about the insect-pathogen-host interactions essential for understanding the physiopathology of the insect bite. The data and information presented in this review aim for the development of new drugs to prevent insect bites and the insect-transmitted endemic of Chagas disease. 相似文献
999.
Rasteiro R Bouttier PA Sousa VC Chikhi L 《Proceedings. Biological sciences / The Royal Society》2012,279(1737):2409-2416
Cultural practices can deeply influence genetic diversity patterns. The Neolithic transitions that took place at different times and locations around the world led to major cultural and demographic changes that influenced and therefore left their marks on human genetic diversity patterns. Several studies on the European Neolithic transition suggest that mitochondrial DNA (mtDNA) and Y-chromosome data can exhibit different patterns, which could be owing to different demographic histories for females and males. Archaeological and anthropological data suggest that the transition from hunter-gatherers (HGs) to farmers' societies is probably associated with changes in social organization, particularly in post-marital residence (PMR) rules (i.e. patrilocality, matrilocality or bilocality). The movements of humans and genes associated with these rules can be seen as sex-biased short-range migrations. We developed a new individual-based simulation approach to explore the genetic consequences of 45 different scenarios, where we varied the patterns of PMR and admixture between HGs and farmers. We recorded mtDNA and Y-chromosome data and analysed their diversity patterns within and between populations, through time and space. We also collected published mtDNA and Y-chromosome data from European and Near-Eastern populations in order to identify the scenarios that would best explain them. We show that: (i) different PMR systems can lead to different patterns of genetic diversity and differentiation, (ii) asymmetries between mtDNA and Y-chromosome can be owing to different behaviours between males and females, but also to different mutations rates, and (iii) patrilocality in farmers explains the present patterns of genetic diversity better than matrilocality or bilocality. Moreover, we found that (iv) the genetic diversity of farmers change depending on the HGs PMR rules even though they are assumed to disappear more than 5000 years ago in our simulations. 相似文献
1000.
Pinheiro A Silva MJ Graça I Silva J Sá R Sousa M Barros A Tavares de Almeida I Rivera I 《Gene》2012,506(1):173-178
During spermatogenesis, germ cells undergo a complex process of cell differentiation and morphological restructuring, which depends on the coordinated expression of different genes. Some vital examples are those involved in cell energy metabolism, namely the genes encoding the E1α subunit of pyruvate dehydrogenase complex: the somatic PDHA1 (X-linked) and the testis-specific PDHA2 (autosomal). There are no data related to the study at the RNA and protein levels of PDHA genes during human spermatogenesis. The present study aimed to describe the mRNA and protein expression patterns of the human PDHA genes during spermatogenesis. Expression profiles of the PDHA1 and PDHA2 genes were characterized using different human tissues and cells. Diploid and haploid germ cells fractions were obtained from testis tissues. The mRNA profiles were analyzed by quantitative RT-PCR, whereas the protein profiles were evaluated by immunohistochemistry, western blotting and two-dimensional electrophoresis. Expression of the PDHA1 gene was found in all somatic cells, whereas expression of PDHA2 gene was restricted to germ cells. The switch from X-linked to autosomic gene expression occurred in spermatocytes. Data suggest the activation of PDHA2 gene expression is most probably a mechanism to ensure the continued expression of the protein, thus allowing germ cell viability and functionality. 相似文献